Anaemia de Fanconi<\/a><\/h3><\/p>\n\n- La Anemia de Fanconi (AF) es un trastorno multisist\u00e9mico caracterizado por un espectro de anomal\u00edas cong\u00e9nitas, insuficiencia progresiva de la m\u00e9dula \u00f3sea y pancitopenia, y predisposici\u00f3n a desarrollar tumores hematol\u00f3gicos y s\u00f3lidos.<\/li>
- La Anemia de Fanconi ocurre en todo el mundo y afecta aproximadamente a 1 de cada 100.000 nacimientos en los EE. UU. Se ha descrito una variabilidad \u00e9tnica, es notablemente m\u00e1s com\u00fan entre los afrik\u00e1ners en Sud\u00e1frica (aproximadamente 1 de cada 22.000), y entre los jud\u00edos asquenaz\u00edes en Israel (1 de cada 45.000). Tambi\u00e9n se ha descrito una prevalencia m\u00e1s alta entre la poblaci\u00f3n gitana espa\u00f1ola.<\/li><\/ul>\n\n
- La Anemia de Fanconi es un s\u00edndrome cl\u00ednicamente heterog\u00e9neo de insuficiencia de la m\u00e9dula \u00f3sea y anomal\u00edas cong\u00e9nitas que pueden afectar a todos los sistemas de \u00f3rganos.<\/li>
- Los pacientes con Anemia de Fanconi pueden sufrir una variedad de malformaciones. Las anomal\u00edas cong\u00e9nitas incluyen malformaciones esquel\u00e9ticas (baja estatura, microcefalia o pulgar hipopl\u00e1sico), anomal\u00edas org\u00e1nicas (renales, oft\u00e1lmicas, auditivas, card\u00edacas y genitales), pigmentaci\u00f3n anormal de la piel, como manchas caf\u00e9 con leche (Tabla 1).<\/li>
- Hasta la fecha, se han implicado al menos 23 genes en la Anemia de Fanconi causada por mutaciones de la l\u00ednea germinal en uno de los m\u00faltiples genes de la Anemia de Fanconi (FANCA a FANCV). Las mutaciones en FANCA son las m\u00e1s comunes y est\u00e1n involucradas en 60 a 65% de los casos. Todas las mutaciones en los genes de la Anemia de Fanconi se heredan de forma autos\u00f3mica recesiva, excepto FANCB y RAD51, que se heredan de forma ligada al cromosoma X y autos\u00f3mica dominante, respectivamente.<\/li>
- Las prote\u00ednas de la Anemia de Fanconi interact\u00faan en una v\u00eda celular com\u00fan y participan en varios aspectos de la reparaci\u00f3n del ADN, particularmente en la reparaci\u00f3n del entrecruzamiento cromos\u00f3mico, la estabilidad gen\u00f3mica y la regulaci\u00f3n de la cascada de prote\u00edna. Los defectos en cualquiera de estas prote\u00ednas de la Anemia de Fanconi dan como resultado inestabilidad gen\u00f3mica, mecanismos defectuosos de reparaci\u00f3n del ADN y un mayor riesgo de c\u00e1ncer.<\/li>
- Los pacientes con Anemia de Fanconi con disfunci\u00f3n hematopoy\u00e9tica generalmente requieren un trasplante de m\u00e9dula \u00f3sea (BMT) o un trasplante de c\u00e9lulas madre hematopoy\u00e9ticas (TCMH), que es la opci\u00f3n de tratamiento preferida.<\/li>
- Una de las complicaciones m\u00e1s comunes despu\u00e9s del trasplante de c\u00e9lulas madre hematopoy\u00e9ticas (TCMH) es el desarrollo de la enfermedad de injerto contra hu\u00e9sped cr\u00f3nica oral (EICHc), que tambi\u00e9n es un factor de riesgo para el desarrollo de c\u00e1ncer, particularmente el carcinoma oral de c\u00e9lulas escamosas. La EICHc se reconoce actualmente como un trastorno oral potencialmente maligno (TOPM)<\/li>
- Dada la amplia gama de anomal\u00edas cl\u00ednicas, los pacientes con Anemia de Fanconi requieren una evaluaci\u00f3n integral en el momento del diagn\u00f3stico.<\/li>
- La expresividad variable de la Anemia de Fanconi hace con que sea dif\u00edcil de distinguir de otros s\u00edndromes gen\u00e9ticos y dificulta el diagn\u00f3stico precoz en determinados casos.
\nLa suma de manifestaciones cl\u00ednicas y las alteraciones hematol\u00f3gicas son, la mayor\u00eda de las veces, orientativas del diagn\u00f3stico.<\/li>
- Moreno et al. (2021) proporcion\u00f3 una descripci\u00f3n cl\u00ednica detallada de las alteraciones m\u00e1s frecuentes encontradas en los diferentes \u00f3rganos.<\/li>
- El diagn\u00f3stico de laboratorio se realiza por positividad en la prueba de rotura cromos\u00f3mica tras la exposici\u00f3n a agentes que inducen los enlaces cruzados entre las cadenas del ADN.
\n
\n<\/li>
- Otros m\u00e9todos de diagn\u00f3stico utilizados incluyen transferencia Western blotting, , amplificaci\u00f3n de sonda dependiente de ligandos m\u00faltiples y secuenciaci\u00f3n de nueva generaci\u00f3n.<\/li>
- Una vez que se confirma el diagn\u00f3stico, se requiere una vigilancia de por vida de los pacientes con Anemia de Fanconi para garantizar un diagn\u00f3stico temprano del c\u00e1ncer. El consejo gen\u00e9tico es fundamental.<\/li><\/ul>\n\n
CARACTER\u00cdSTICAS CL\u00cdNICA DE LA ANEMIA DE FANCONI<\/strong>
(adaptado de Nalepa and Clapp 2018) <\/p>\n\n<\/div>\n\n\n\n- Malformaciones craneofaciales<\/li>
- Retraso del desarrollo<\/li>
- Estatura baja<\/li>
- Hipodoncia, microdoncia<\/li>
- Hemorragia oral<\/li>
- Hinchaz\u00f3n gingival<\/li>
- Asociaci\u00f3n VACTERL<\/li>
- Pulgar o radio anormal<\/li><\/ul>\n<\/div>\n\n\n\n\n
- Osteoporosis<\/li>
- Insuficiencia progresiva de la m\u00e9dula \u00f3sea <\/li>
- Defectos card\u00edacos<\/li>
- Malformaciones genitourinarias y gastrointestinales<\/li>
- Ectopia o displasia renal<\/li>
- Disfunci\u00f3n end\u00f3crina<\/li>
- Disminuci\u00f3n de la fertilidad<\/li><\/ul>\n<\/div>\n<\/div>\n\n
- Alrededor de una cuarta parte de los pacientes con Anemia de Fanconi que desarrollan tumores s\u00f3lidos reciben el diagn\u00f3stico de Anemia de Fanconi despu\u00e9s del descubrimiento de su c\u00e1ncer.<\/li>
- Por lo tanto, se debe considerar la Anemia de Fanconi en neoplasias malignas de aparici\u00f3n temprana. La aparici\u00f3n temprana del c\u00e1ncer oral como se describe en varios informes de casos (citados a continuaci\u00f3n) puede servir como indicador para considerar el diagn\u00f3stico de Anemia de Fanconi en pacientes j\u00f3venes que desarrollan carcinomas de c\u00e9lulas escamosas de cabeza y cuello en ausencia de factores de riesgo.<\/li>
- La Anemia de Fanconi puede provocar insuficiencia de la m\u00e9dula \u00f3sea, a su vez el trasplante de c\u00e9lulas madre hematopoy\u00e9ticas puede provocar EICHc.<\/li>
- La incidencia estimada de desarrollar un carcinoma oral de c\u00e9lulas escamosas es de 200 a 800 veces mayor en pacientes con Anemia de Fanconi que en la poblaci\u00f3n general. Recientemente, ha habido un renovado inter\u00e9s entre los investigadores sobre el desarrollo del carcinoma oral de c\u00e9lulas escamosas en en la Anemia de Fanconi.<\/li>
- En una revisi\u00f3n de los casos de Anemia de Fanconi publicados, la media de edad de los 12 pacientes que desarrollaron carcinomas orales despu\u00e9s de un trasplante de m\u00e9dula \u00f3sea fue de 21 a\u00f1os, significativamente menor que la edad de 28 de los pacientes que no hab\u00edan recibido un trasplante de m\u00e9dula \u00f3sea (P < 0,02). , lo que sugiere un posible efecto adverso del trasplante, es decir, EICHc, sobre el riesgo de desarrollar un carcinoma oral (Alter, 2003)<\/li>
- Masserot et al., (2008) describieron la serie m\u00e1s grande hasta el momento de carcinomas de c\u00e9lulas escamosas de cabeza y cuello, 13 pacientes (8 en la cavidad oral) con anemia de Fanconi despu\u00e9s de un trasplante de c\u00e9lulas madre hematopoy\u00e9ticas (TCMH). La aparici\u00f3n de un carcinoma de c\u00e9lulas escamosas de la lengua en una persona joven que no fuma debe hacer que se considere la Anemia de Fanconi como la afecci\u00f3n m\u00e9dica subyacente y debe dar lugar a la realizaci\u00f3n de una prueba de detecci\u00f3n de rotura cromos\u00f3mica.<\/li><\/ul>\n
<\/div><\/div>\n\n
Disqueratosis Cong\u00e9nita<\/a><\/h3><\/p>\n\n\nDyskeratosis congenita (DC) is a rare multisystem inherited genodermatosis leading to reduced telemerase function impairing chromosomal stability. Also known as Zinsser-Cole-Engman syndrome, it was first described in 1906 . Telemeres form the ends of chromosomes and telemerase is an enzyme responsible for the synthesis of telomeres. A reduction in or impaired function of telemerase leads to a reduction in genetic material and subsequent activation of \u2018DNA damage response pathways\u2019 resulting in cell death. <\/p>\n\n\n\n
Bone marrow failure occurs as the bone marrow is dependent on telomere function due to its high cell turnover. In addition, DC also commonly manifests with mucocutaneous signs, pulmonary and\/or hepatic fibrosis.<\/p>\n\n\n\n
Aetiology<\/a><\/h3><\/div><\/div><\/p>\n\n\n\n- Dyskeratosis congenita is one of a few inherited marrow failure syndromes which has inheritance patterns including X-linked, autosomal dominant and autosomal recessive. <\/li>
- The specific genetic defect DKC1 mutation associated with X-linked DC, the most severe form of DC, leads to absence of functioning dyskerin, severely impairing telemerase function. <\/li>
- A number of genetic mutations have been identified resulting in different clinical manifestations including RTEL1 and TINF2 which have cerebellar hypoplasia and retinal disease as prominent features, respectively. <\/li>
- Recessive mutations in NOP10, CTC1, NHP2, PARN and WRAP53 are rarer and lead to differing clinical presentations. <\/li><\/ul>\n\n\n
<\/div><\/div>\n\n\n\n
Epidemiology<\/a><\/h3><\/p>\n\n\n\n- Dyskeratosis congenita is rare, typically presenting clinically between 5-12 years and has a male predominance. <\/li>
- An estimated incidence of 1 in 1000000 people has been reported. <\/li><\/ul>\n\n\n
<\/div><\/div>\n\n\n\n
Clinical Presentation<\/a><\/h3> <\/p>\n\n\n\n- The presentation of DC is typically early in life, in contrast to acquired forms of aplastic anaemia and are the consequence of the genetic mutations . <\/li>
- Zinsser in 1906 first described the characteristic triad of DC which includes the following:<\/li><\/ul>\n\n\n\n
- Reticular atrophy and cutaneous hyperpigmentation <\/li>
- Nail dystrophy (Figure 1)<\/li>
- Oral leukoplakia <\/li><\/ul>\n\n\n\n
- In patients with DC as a result of chromosomal instability, there is an increased risk of developing cancer affecting various bodily systems. <\/li>
- It has been reported that children with DC have a 100-fold increased risk of developing Acute Myeloid Leukaemia (AML). <\/li>
- There is also an increased risk of developing squamous cell carcinomas of the head and neck, cervix and anogenital region. <\/li>
- Cancers of the skin, aerodigestive tract and pancreas have also been reported and majority of all cancers occur in third decade of age. <\/li><\/ul>\n\n\n
<\/div><\/div>\n\n\n\n
Oral Manifestations<\/a><\/h3><\/p>\n\n\n\n- A number of intraoral changes have been reported to present in patients with DC including oral leukoplakia, which is the most common feature found in up to 80% of patients . <\/li>
- The most common sites involved are the tongue, buccal mucosa, palate and gingivae. <\/li>
- There can also be soft tissue changes including erythema, particularly in the buccal mucosa and tongue, brown pigmentation, and depapillation of the tongue. <\/li>
- In addition, altered sensation described as burning of the tongue has been reported <\/li><\/ul>\n\n\n\n
Dental Implications:<\/strong><\/em><\/p>\n\n\n\n- Gingival inflammation and periodontal disease are frequently seen in patients with DC due to a combination of early destruction of periodontal tissues as a result of anomalies in ectodermal derived structures, and a poor response to this secondary to neutropenia. <\/li>
- Dental caries is frequently identified in patients with DC with one study of 73 patients reporting \u2018extensive caries\u2019 in 13 patients and these findings have been supported elsewhere.<\/li>
- Other dental anomalies seen in patients with DC include hypodontia, short blunted roots, thinned enamel, taurodontism, decreased crown\/root ratio, hypocalcification and gingival recession. <\/li><\/ul>\n\n\n\n
Malignant Transformation:<\/strong><\/em><\/p>\n\n\n\n- The rate of malignant transformation of oral leukoplakia has been documented to range between 0.13-34% depending on multiple risk factors such as age, sex, homogeneity and size of the lesion. <\/li>
- In DC, the rate of progression of such lesions to cancer is approximately 30% between 10-30 years. <\/li>
- Moreover, in DC due to early telomere shortening, cancers have been reported to present earlier in patients as young as 5 years. Therefore, close surveillance is essential and frequently require biopsies. <\/li><\/ul>\n\n\n
<\/div><\/div>\n\n\n\n
Differential diagnosis<\/a><\/h3> <\/p>\n\n\n\nAplastic anaemia can be classified into two broad categories; acquired and inherited. The acquired causes include idiopathic, which is the most common cause, drug induced, viral, pregnancy and connective tissue diseases. Inherited causes include Fanconi anaemia, Shwachman- Diamond Syndrome and GATA2 syndrome. Though Fanconi anaemia remains the most common differential diagnosis. <\/p>\n\n\n\n
Differential diagnoses oral white lesions involve infective processes such as candidiasis and non-infective causes including oral lichen planus, lichenoid lesions, white sponge naevus, frictional keratosis and graft-versus-host disease GVHD. <\/p>\n\n\n
<\/div><\/div>\n\n\n\n
Diagnosis<\/a><\/h3><\/p>\n\n\n\n- The diagnostic criteria for DC as outlined by Dokal 2011 states that at least 2 of 4 major features (BM failure, abnormal skin pigmentation, nail dystrophy and leukoplakia) must be present along with a minimum of at least two other identified somatic features. These are shown in the table 1.<\/strong><\/li>
- The diagnosis of DC can be confirmed by performing blood tests including full blood count (FBC) and reticulocyte count to establish if pancytopenia is present. <\/li>
- A bone marrow biopsy may reveal a hypocellular marrow. <\/li>
- Further investigations would include specialised tests such as genetic sequencing, measurement of telomere length by flow cytometry fluorescence in situ hybridisation (FISH) and computed tomography (CT) scans to determine if pulmonary and\/or hepatic involvement. <\/li>
- In the case of a positive family history, prenatal genetic diagnosis by chorionic villus sampling or preimplantation genetic diagnosis may be available.<\/li><\/ul>\n\n\n
<\/div><\/div>\n\n\n\n
Management<\/a><\/h3><\/p>\n\n\n\n- Multidisciplinary (MDT) approach is required in the care of patient\u2019s diagnosed with DC and the health care professionals involved will be governed by the bodily systems involved.<\/li>
- Haematologists will have a focal role as bone marrow failure is a primary cause of early morbidity and mortality. <\/li>
- Oral leukoplakia particularly in patients with DC has the potential to transform into oral cancer and therefore attentive surveillance is required. <\/li>
- A holistic approach in preventing and managing dental disease through optimised preventative advice and interventions are essential in improving quality of life for patients with DC. <\/li><\/ul>\n\n\n\n
\u00bb Non-Surgical Management<\/p>
<\/p>\n\n\n\nNon-Surgical Management<\/strong><\/p>\n\n\n\nNon-surgical management of oral leukoplakia with topical tretinoin 0.1% solution<\/strong> resulted in partial improvement in two siblings aged 10 and 15 years old. Chemotherapeutic agents such as bleomycin and cyclophosphamide<\/strong> have been reported to be effective but similar results have not shown to be consistent in improving oral leukoplakia. Another reported etretinate, a vitamin A derivative<\/strong>, was effective for oral leukoplakia in DC. <\/p>\n\n\n
\u00bb View less<\/p><\/div><\/div><\/p>\n\n\n\n
\u00bb Surgical Management<\/p>
<\/p>\n\n\n\nSurgical Management<\/strong><\/p>\n\n\n\nOral and maxillofacial surgeons may decide to surgically intervene if atypia or squamous cell carcinoma is detected. Resections of oral soft and hard tissue will often require reconstruction with prosthesis, therefore necessitating detailed planning with a prosthodontist to achieve a satisfactory functional and aesthetic result. <\/p>\n\n\n\n
- La Anemia de Fanconi (AF) es un trastorno multisist\u00e9mico caracterizado por un espectro de anomal\u00edas cong\u00e9nitas, insuficiencia progresiva de la m\u00e9dula \u00f3sea y pancitopenia, y predisposici\u00f3n a desarrollar tumores hematol\u00f3gicos y s\u00f3lidos.<\/li>
- La Anemia de Fanconi ocurre en todo el mundo y afecta aproximadamente a 1 de cada 100.000 nacimientos en los EE. UU. Se ha descrito una variabilidad \u00e9tnica, es notablemente m\u00e1s com\u00fan entre los afrik\u00e1ners en Sud\u00e1frica (aproximadamente 1 de cada 22.000), y entre los jud\u00edos asquenaz\u00edes en Israel (1 de cada 45.000). Tambi\u00e9n se ha descrito una prevalencia m\u00e1s alta entre la poblaci\u00f3n gitana espa\u00f1ola.<\/li><\/ul>\n\n
- La Anemia de Fanconi es un s\u00edndrome cl\u00ednicamente heterog\u00e9neo de insuficiencia de la m\u00e9dula \u00f3sea y anomal\u00edas cong\u00e9nitas que pueden afectar a todos los sistemas de \u00f3rganos.<\/li>
- Los pacientes con Anemia de Fanconi pueden sufrir una variedad de malformaciones. Las anomal\u00edas cong\u00e9nitas incluyen malformaciones esquel\u00e9ticas (baja estatura, microcefalia o pulgar hipopl\u00e1sico), anomal\u00edas org\u00e1nicas (renales, oft\u00e1lmicas, auditivas, card\u00edacas y genitales), pigmentaci\u00f3n anormal de la piel, como manchas caf\u00e9 con leche (Tabla 1).<\/li>
- Hasta la fecha, se han implicado al menos 23 genes en la Anemia de Fanconi causada por mutaciones de la l\u00ednea germinal en uno de los m\u00faltiples genes de la Anemia de Fanconi (FANCA a FANCV). Las mutaciones en FANCA son las m\u00e1s comunes y est\u00e1n involucradas en 60 a 65% de los casos. Todas las mutaciones en los genes de la Anemia de Fanconi se heredan de forma autos\u00f3mica recesiva, excepto FANCB y RAD51, que se heredan de forma ligada al cromosoma X y autos\u00f3mica dominante, respectivamente.<\/li>
- Las prote\u00ednas de la Anemia de Fanconi interact\u00faan en una v\u00eda celular com\u00fan y participan en varios aspectos de la reparaci\u00f3n del ADN, particularmente en la reparaci\u00f3n del entrecruzamiento cromos\u00f3mico, la estabilidad gen\u00f3mica y la regulaci\u00f3n de la cascada de prote\u00edna. Los defectos en cualquiera de estas prote\u00ednas de la Anemia de Fanconi dan como resultado inestabilidad gen\u00f3mica, mecanismos defectuosos de reparaci\u00f3n del ADN y un mayor riesgo de c\u00e1ncer.<\/li>
- Los pacientes con Anemia de Fanconi con disfunci\u00f3n hematopoy\u00e9tica generalmente requieren un trasplante de m\u00e9dula \u00f3sea (BMT) o un trasplante de c\u00e9lulas madre hematopoy\u00e9ticas (TCMH), que es la opci\u00f3n de tratamiento preferida.<\/li>
- Una de las complicaciones m\u00e1s comunes despu\u00e9s del trasplante de c\u00e9lulas madre hematopoy\u00e9ticas (TCMH) es el desarrollo de la enfermedad de injerto contra hu\u00e9sped cr\u00f3nica oral (EICHc), que tambi\u00e9n es un factor de riesgo para el desarrollo de c\u00e1ncer, particularmente el carcinoma oral de c\u00e9lulas escamosas. La EICHc se reconoce actualmente como un trastorno oral potencialmente maligno (TOPM)<\/li>
- Dada la amplia gama de anomal\u00edas cl\u00ednicas, los pacientes con Anemia de Fanconi requieren una evaluaci\u00f3n integral en el momento del diagn\u00f3stico.<\/li>
- La expresividad variable de la Anemia de Fanconi hace con que sea dif\u00edcil de distinguir de otros s\u00edndromes gen\u00e9ticos y dificulta el diagn\u00f3stico precoz en determinados casos. \nLa suma de manifestaciones cl\u00ednicas y las alteraciones hematol\u00f3gicas son, la mayor\u00eda de las veces, orientativas del diagn\u00f3stico.<\/li>
- Moreno et al. (2021) proporcion\u00f3 una descripci\u00f3n cl\u00ednica detallada de las alteraciones m\u00e1s frecuentes encontradas en los diferentes \u00f3rganos.<\/li>
- El diagn\u00f3stico de laboratorio se realiza por positividad en la prueba de rotura cromos\u00f3mica tras la exposici\u00f3n a agentes que inducen los enlaces cruzados entre las cadenas del ADN. \n \n<\/li>
- Otros m\u00e9todos de diagn\u00f3stico utilizados incluyen transferencia Western blotting, , amplificaci\u00f3n de sonda dependiente de ligandos m\u00faltiples y secuenciaci\u00f3n de nueva generaci\u00f3n.<\/li>
- Una vez que se confirma el diagn\u00f3stico, se requiere una vigilancia de por vida de los pacientes con Anemia de Fanconi para garantizar un diagn\u00f3stico temprano del c\u00e1ncer. El consejo gen\u00e9tico es fundamental.<\/li><\/ul>\n\n
CARACTER\u00cdSTICAS CL\u00cdNICA DE LA ANEMIA DE FANCONI<\/strong>
(adaptado de Nalepa and Clapp 2018) <\/p>\n\n<\/div>\n\n\n\n- Malformaciones craneofaciales<\/li>
- Retraso del desarrollo<\/li>
- Estatura baja<\/li>
- Hipodoncia, microdoncia<\/li>
- Hemorragia oral<\/li>
- Hinchaz\u00f3n gingival<\/li>
- Asociaci\u00f3n VACTERL<\/li>
- Pulgar o radio anormal<\/li><\/ul>\n<\/div>\n\n\n\n\n
- Osteoporosis<\/li>
- Insuficiencia progresiva de la m\u00e9dula \u00f3sea <\/li>
- Defectos card\u00edacos<\/li>
- Malformaciones genitourinarias y gastrointestinales<\/li>
- Ectopia o displasia renal<\/li>
- Disfunci\u00f3n end\u00f3crina<\/li>
- Disminuci\u00f3n de la fertilidad<\/li><\/ul>\n<\/div>\n<\/div>\n\n
- Alrededor de una cuarta parte de los pacientes con Anemia de Fanconi que desarrollan tumores s\u00f3lidos reciben el diagn\u00f3stico de Anemia de Fanconi despu\u00e9s del descubrimiento de su c\u00e1ncer.<\/li>
- Por lo tanto, se debe considerar la Anemia de Fanconi en neoplasias malignas de aparici\u00f3n temprana. La aparici\u00f3n temprana del c\u00e1ncer oral como se describe en varios informes de casos (citados a continuaci\u00f3n) puede servir como indicador para considerar el diagn\u00f3stico de Anemia de Fanconi en pacientes j\u00f3venes que desarrollan carcinomas de c\u00e9lulas escamosas de cabeza y cuello en ausencia de factores de riesgo.<\/li>
- La Anemia de Fanconi puede provocar insuficiencia de la m\u00e9dula \u00f3sea, a su vez el trasplante de c\u00e9lulas madre hematopoy\u00e9ticas puede provocar EICHc.<\/li>
- La incidencia estimada de desarrollar un carcinoma oral de c\u00e9lulas escamosas es de 200 a 800 veces mayor en pacientes con Anemia de Fanconi que en la poblaci\u00f3n general. Recientemente, ha habido un renovado inter\u00e9s entre los investigadores sobre el desarrollo del carcinoma oral de c\u00e9lulas escamosas en en la Anemia de Fanconi.<\/li>
- En una revisi\u00f3n de los casos de Anemia de Fanconi publicados, la media de edad de los 12 pacientes que desarrollaron carcinomas orales despu\u00e9s de un trasplante de m\u00e9dula \u00f3sea fue de 21 a\u00f1os, significativamente menor que la edad de 28 de los pacientes que no hab\u00edan recibido un trasplante de m\u00e9dula \u00f3sea (P < 0,02). , lo que sugiere un posible efecto adverso del trasplante, es decir, EICHc, sobre el riesgo de desarrollar un carcinoma oral (Alter, 2003)<\/li>
- Masserot et al., (2008) describieron la serie m\u00e1s grande hasta el momento de carcinomas de c\u00e9lulas escamosas de cabeza y cuello, 13 pacientes (8 en la cavidad oral) con anemia de Fanconi despu\u00e9s de un trasplante de c\u00e9lulas madre hematopoy\u00e9ticas (TCMH). La aparici\u00f3n de un carcinoma de c\u00e9lulas escamosas de la lengua en una persona joven que no fuma debe hacer que se considere la Anemia de Fanconi como la afecci\u00f3n m\u00e9dica subyacente y debe dar lugar a la realizaci\u00f3n de una prueba de detecci\u00f3n de rotura cromos\u00f3mica.<\/li><\/ul>\n
<\/div><\/div>\n\n
Disqueratosis Cong\u00e9nita<\/a><\/h3>
<\/p>\n\n\nDyskeratosis congenita (DC) is a rare multisystem inherited genodermatosis leading to reduced telemerase function impairing chromosomal stability. Also known as Zinsser-Cole-Engman syndrome, it was first described in 1906 . Telemeres form the ends of chromosomes and telemerase is an enzyme responsible for the synthesis of telomeres. A reduction in or impaired function of telemerase leads to a reduction in genetic material and subsequent activation of \u2018DNA damage response pathways\u2019 resulting in cell death. <\/p>\n\n\n\n
Bone marrow failure occurs as the bone marrow is dependent on telomere function due to its high cell turnover. In addition, DC also commonly manifests with mucocutaneous signs, pulmonary and\/or hepatic fibrosis.<\/p>\n\n\n\n
Aetiology<\/a><\/h3>
<\/div><\/div><\/p>\n\n\n\n- Dyskeratosis congenita is one of a few inherited marrow failure syndromes which has inheritance patterns including X-linked, autosomal dominant and autosomal recessive. <\/li>
- The specific genetic defect DKC1 mutation associated with X-linked DC, the most severe form of DC, leads to absence of functioning dyskerin, severely impairing telemerase function. <\/li>
- A number of genetic mutations have been identified resulting in different clinical manifestations including RTEL1 and TINF2 which have cerebellar hypoplasia and retinal disease as prominent features, respectively. <\/li>
- Recessive mutations in NOP10, CTC1, NHP2, PARN and WRAP53 are rarer and lead to differing clinical presentations. <\/li><\/ul>\n\n\n
<\/div><\/div>\n\n\n\n
Epidemiology<\/a><\/h3>
<\/p>\n\n\n\n- Dyskeratosis congenita is rare, typically presenting clinically between 5-12 years and has a male predominance. <\/li>
- An estimated incidence of 1 in 1000000 people has been reported. <\/li><\/ul>\n\n\n
<\/div><\/div>\n\n\n\n
Clinical Presentation<\/a><\/h3>
<\/p>\n\n\n\n- The presentation of DC is typically early in life, in contrast to acquired forms of aplastic anaemia and are the consequence of the genetic mutations . <\/li>
- Zinsser in 1906 first described the characteristic triad of DC which includes the following:<\/li><\/ul>\n\n\n\n
- Reticular atrophy and cutaneous hyperpigmentation <\/li>
- Nail dystrophy (Figure 1)<\/li>
- Oral leukoplakia <\/li><\/ul>\n\n\n\n
- In patients with DC as a result of chromosomal instability, there is an increased risk of developing cancer affecting various bodily systems. <\/li>
- It has been reported that children with DC have a 100-fold increased risk of developing Acute Myeloid Leukaemia (AML). <\/li>
- There is also an increased risk of developing squamous cell carcinomas of the head and neck, cervix and anogenital region. <\/li>
- Cancers of the skin, aerodigestive tract and pancreas have also been reported and majority of all cancers occur in third decade of age. <\/li><\/ul>\n\n\n
<\/div><\/div>\n\n\n\n
Oral Manifestations<\/a><\/h3>
<\/p>\n\n\n\n- A number of intraoral changes have been reported to present in patients with DC including oral leukoplakia, which is the most common feature found in up to 80% of patients . <\/li>
- The most common sites involved are the tongue, buccal mucosa, palate and gingivae. <\/li>
- There can also be soft tissue changes including erythema, particularly in the buccal mucosa and tongue, brown pigmentation, and depapillation of the tongue. <\/li>
- In addition, altered sensation described as burning of the tongue has been reported <\/li><\/ul>\n\n\n\n
Dental Implications:<\/strong><\/em><\/p>\n\n\n\n
- Gingival inflammation and periodontal disease are frequently seen in patients with DC due to a combination of early destruction of periodontal tissues as a result of anomalies in ectodermal derived structures, and a poor response to this secondary to neutropenia. <\/li>
- Dental caries is frequently identified in patients with DC with one study of 73 patients reporting \u2018extensive caries\u2019 in 13 patients and these findings have been supported elsewhere.<\/li>
- Other dental anomalies seen in patients with DC include hypodontia, short blunted roots, thinned enamel, taurodontism, decreased crown\/root ratio, hypocalcification and gingival recession. <\/li><\/ul>\n\n\n\n
Malignant Transformation:<\/strong><\/em><\/p>\n\n\n\n
- The rate of malignant transformation of oral leukoplakia has been documented to range between 0.13-34% depending on multiple risk factors such as age, sex, homogeneity and size of the lesion. <\/li>
- In DC, the rate of progression of such lesions to cancer is approximately 30% between 10-30 years. <\/li>
- Moreover, in DC due to early telomere shortening, cancers have been reported to present earlier in patients as young as 5 years. Therefore, close surveillance is essential and frequently require biopsies. <\/li><\/ul>\n\n\n
<\/div><\/div>\n\n\n\n
Differential diagnosis<\/a><\/h3>
<\/p>\n\n\n\nAplastic anaemia can be classified into two broad categories; acquired and inherited. The acquired causes include idiopathic, which is the most common cause, drug induced, viral, pregnancy and connective tissue diseases. Inherited causes include Fanconi anaemia, Shwachman- Diamond Syndrome and GATA2 syndrome. Though Fanconi anaemia remains the most common differential diagnosis. <\/p>\n\n\n\n
Differential diagnoses oral white lesions involve infective processes such as candidiasis and non-infective causes including oral lichen planus, lichenoid lesions, white sponge naevus, frictional keratosis and graft-versus-host disease GVHD. <\/p>\n\n\n
<\/div><\/div>\n\n\n\n
Diagnosis<\/a><\/h3>
<\/p>\n\n\n\n- The diagnostic criteria for DC as outlined by Dokal 2011 states that at least 2 of 4 major features (BM failure, abnormal skin pigmentation, nail dystrophy and leukoplakia) must be present along with a minimum of at least two other identified somatic features. These are shown in the table 1.<\/strong><\/li>
- The diagnosis of DC can be confirmed by performing blood tests including full blood count (FBC) and reticulocyte count to establish if pancytopenia is present. <\/li>
- A bone marrow biopsy may reveal a hypocellular marrow. <\/li>
- Further investigations would include specialised tests such as genetic sequencing, measurement of telomere length by flow cytometry fluorescence in situ hybridisation (FISH) and computed tomography (CT) scans to determine if pulmonary and\/or hepatic involvement. <\/li>
- In the case of a positive family history, prenatal genetic diagnosis by chorionic villus sampling or preimplantation genetic diagnosis may be available.<\/li><\/ul>\n\n\n
<\/div><\/div>\n\n\n\n
Management<\/a><\/h3>
<\/p>\n\n\n\n- Multidisciplinary (MDT) approach is required in the care of patient\u2019s diagnosed with DC and the health care professionals involved will be governed by the bodily systems involved.<\/li>
- Haematologists will have a focal role as bone marrow failure is a primary cause of early morbidity and mortality. <\/li>
- Oral leukoplakia particularly in patients with DC has the potential to transform into oral cancer and therefore attentive surveillance is required. <\/li>
- A holistic approach in preventing and managing dental disease through optimised preventative advice and interventions are essential in improving quality of life for patients with DC. <\/li><\/ul>\n\n\n\n
\u00bb Non-Surgical Management<\/p>
<\/p>\n\n\n\nNon-Surgical Management<\/strong><\/p>\n\n\n\n
Non-surgical management of oral leukoplakia with topical tretinoin 0.1% solution<\/strong> resulted in partial improvement in two siblings aged 10 and 15 years old. Chemotherapeutic agents such as bleomycin and cyclophosphamide<\/strong> have been reported to be effective but similar results have not shown to be consistent in improving oral leukoplakia. Another reported etretinate, a vitamin A derivative<\/strong>, was effective for oral leukoplakia in DC. <\/p>\n\n\n
\u00bb View less<\/p><\/div><\/div><\/p>\n\n\n\n
\u00bb Surgical Management<\/p>
<\/p>\n\n\n\nSurgical Management<\/strong><\/p>\n\n\n\n
Oral and maxillofacial surgeons may decide to surgically intervene if atypia or squamous cell carcinoma is detected. Resections of oral soft and hard tissue will often require reconstruction with prosthesis, therefore necessitating detailed planning with a prosthodontist to achieve a satisfactory functional and aesthetic result. <\/p>\n\n\n\n
- The diagnostic criteria for DC as outlined by Dokal 2011 states that at least 2 of 4 major features (BM failure, abnormal skin pigmentation, nail dystrophy and leukoplakia) must be present along with a minimum of at least two other identified somatic features. These are shown in the table 1.<\/strong><\/li>
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